Emerging studies have shown that epitranscriptomic RNA modifications play a crucial role in processes such as cell differentiation, embryonic development, drug resistance, and tumorigenesis through post‐transcriptional gene regulation.[3, 24] For instance, YBX1 facilitates the ESCC progression via m5C‐dependent SMOX mRNA.[25] However, as a newly identified epigenetic modification within mRNA, the biological function of ac4C modification remains largely unknown. Here, SMOX is linked to esophageal squamous cell carcinoma.